{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T21:47:29Z","timestamp":1785880049123,"version":"3.56.0"},"reference-count":12,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000030","name":"US Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["U01GH002238"],"award-info":[{"award-number":["U01GH002238"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000030","name":"US Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["1193826"],"award-info":[{"award-number":["1193826"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Australian National Health and Medical Research Council (NHMRC) Fellowship","award":["U01GH002238"],"award-info":[{"award-number":["U01GH002238"]}]},{"name":"Australian National Health and Medical Research Council (NHMRC) Fellowship","award":["1193826"],"award-info":[{"award-number":["1193826"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Leptospirosis is a zoonotic disease caused by Leptospira spp., with over 250 serovars classified into 24 serogroups. Control measures depend on understanding serovar-specific epidemiology, yet the microscopic agglutination test (MAT) is only serogroup specific, and classification is complicated by cross-reactivity. While MAT is the reference standard for leptospirosis serodiagnosis and seroepidemiological studies, factors influencing serogroup cross-reactivity remain poorly characterized. We investigated the relationship between age, antibody titer, and serogroup diversity among seropositive individuals in a population-based serosurvey in the Dominican Republic. Between June and October 2021, we conducted a multistage national serosurvey, enrolling 6683 participants across 134 clusters. MAT was performed on sera from 2091 participants in two provinces using a 20-serovar panel. MAT positivity was defined as titers \u2265 1:100. Generalized Additive Models were used to assess associations between age, maximum titer, and serogroup diversity. Of 2091 tested samples, 237 (11.3%) were seropositive. Older individuals and those with higher titers reacted to a greater number of serogroups (p = 0.005 and p &lt; 0.0001, respectively). However, mean maximum titer decreased with age, suggesting that broader serogroup reactivity in older individuals reflects cumulative exposure rather than higher titers. Maximum titer was the strongest predictor of serogroup breadth, while gender, study region, and urban\/rural setting were not significant. Overall, our findings demonstrate that serogroup cross-reactivity in MAT was significantly influenced by antibody titer and prior exposure, with older individuals displaying broader serogroup reactivity despite lower titers. These findings highlight key considerations for interpreting MAT results in seroepidemiological studies and underscore the limitations of MAT in serogroup-level classification.<\/jats:p>","DOI":"10.3390\/tropicalmed10100275","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T09:43:12Z","timestamp":1758706992000},"page":"275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Deciphering Microscopic Agglutination Test (MAT) Serogroup Cross-Reactivity in Leptospirosis: The Influence of Age and Antibody Titers"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7044-5257","authenticated-orcid":false,"given":"Eric J.","family":"Nilles","sequence":"first","affiliation":[{"name":"Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"},{"name":"Harvard Medical School, Boston, MA 02115, USA"},{"name":"Harvard Humanitarian Initiative, Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Then Paulino","sequence":"additional","affiliation":[{"name":"Ministry of Health and Social Assistance, Santo Domingo 10514, Dominican Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Duke","sequence":"additional","affiliation":[{"name":"Pedro Henr\u00edquez Ure\u00f1a National University, Santo Domingo 10514, Dominican Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Skewes-Ramm","sequence":"additional","affiliation":[{"name":"Ministry of Health and Social Assistance, Santo Domingo 10514, Dominican Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Kucharski","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Epidemiology and Dynamics, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8288-4169","authenticated-orcid":false,"given":"Colleen L.","family":"Lau","sequence":"additional","affiliation":[{"name":"University of Queensland Centre of Clinical Research (UQCCR), The University of Queensland, Brisbane, QLD 4029, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1097\/QCO.0b013e32814a5729","article-title":"Leptospirosis: Pathogenesis, immunity, and diagnosis","volume":"20","author":"Palaniappan","year":"2007","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"450","DOI":"10.7589\/2017-10-269","article-title":"Leptospira antibodies detected in wildlife in the USA and the US Virgin Islands","volume":"54","author":"Pedersen","year":"2018","journal-title":"J. Wildl. Dis."},{"key":"ref_3","first-page":"100390","article-title":"SARS-CoV-2 seroprevalence, cumulative infections, and immunity to symptomatic infection\u2014A multistage national household survey and modelling study, Dominican Republic, June\u2013October 2021","volume":"16","author":"Nilles","year":"2022","journal-title":"Lancet Reg. Health\u2014Am."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nilles, E.J., Paulino, C.T., Galloway, R., Aubin, M.d.S., Mayfield, H.J., Restrepo, A.C., Dumas, D., Garnier, S., Etienne, M.C., and Duke, W. (2024). Seroepidemiology of human leptospirosis in the Dominican Republic: A multistage cluster survey, 2021. PLoS Negl. Trop. Dis., 18.","DOI":"10.1371\/journal.pntd.0012463"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Martin, B.M., Sartorius, B., Mayfield, H.J., Restrepo, A.M.C., Kiani, B., Paulino, C.J.T., Etienne, M.C., Skewes-Ramm, R., Aubin, M.d.S., and Dumas, D. (2025). Quantifying spatial variation in environmental and sociodemographic drivers of leptospirosis in the Dominican Republic using a geographically weighted regression model. Sci. Rep., 5.","DOI":"10.21203\/rs.3.rs-6449611\/v1"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Martin, B.M., Sartorius, B., Mayfield, H.J., Restrepo, A.M.C., Kiani, B., Paulino, C.J.T., Etienne, M.C., Skewes-Ramm, R., Aubin, M.d.S., and Dumas, D. (2025). Geospatial analysis of leptospirosis clusters and risk factors in two provinces of the Dominican Republic. PLoS Negl. Trop. Dis., 19.","DOI":"10.1371\/journal.pntd.0013103"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"723","DOI":"10.3201\/eid2904.221628","article-title":"Monitoring Temporal Changes in SARS-CoV-2 Spike Antibody Levels and Variant-Specific Risk for Infection, Dominican Republic, March 2021\u2013August 2022","volume":"29","author":"Nilles","year":"2023","journal-title":"Emerg. Infect. Dis. J."},{"key":"ref_8","unstructured":"R Core Team (2021). R: A language and environment for statistical computing. R Foundation for Statistical Computing, R Core Team."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wickham, H. (2016). ggplot2: Elegant Graphics for Data Analysis, Springer.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41420-024-01889-5","article-title":"B cell memory: From generation to reactivation: A multipronged defense wall against pathogens","volume":"10","author":"Syeda","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1086\/346208","article-title":"Usefulness of serologic analysis as a predictor of the infecting serovar in patients with severe leptospirosis","volume":"36","author":"Levett","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pntd.0012042","article-title":"Navigating cross-reactivity and host species effects in a serological assay: A case study of the microscopic agglutination test for Leptospira serology","volume":"18","author":"Mummah","year":"2024","journal-title":"PLoS Negl. Trop. Dis."}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/10\/10\/275\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:48:41Z","timestamp":1760035721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/10\/10\/275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,24]]},"references-count":12,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["tropicalmed10100275"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed10100275","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,24]]}}}